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Cited by 33Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The DOI matches its Crossref record; 229 of the 232 references it cites were found in a registry or an index.

Neuroimaging of Mouse Models of Alzheimer’s Disease

Open access
Jullienne, Amandine, Trinh, Michelle V., Obenaus, Andre·2022·Biomedicines
DOI 10.3390/biomedicines10020305PMC PMC8869427
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Abstract

Magnetic resonance imaging (MRI) and positron emission tomography (PET) have made great strides in the diagnosis and our understanding of Alzheimer’s Disease (AD). Despite the knowledge gained from human studies, mouse models have and continue to play an important role in deciphering the cellular and molecular evolution of AD. MRI and PET are now being increasingly used to investigate neuroimaging features in mouse models and provide the basis for rapid translation to the clinical setting. Here, we provide an overview of the human MRI and PET imaging landscape as a prelude to an in-depth review of preclinical imaging in mice. A broad range of mouse models recapitulate certain aspects of the human AD, but no single model simulates the human disease spectrum. We focused on the two of the most popular mouse models, the 3xTg-AD and the 5xFAD models, and we summarized all known published MRI and PET imaging data, including contrasting findings. The goal of this review is to provide the reader with broad framework to guide future studies in existing and future mouse models of AD. We also highlight aspects of MRI and PET imaging that could be improved to increase rigor and reproducibility in future imaging studies.

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Crossref · 10.3390/biomedicines10020305

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Figure 1 Pubmed citations for 5xFAD and 3xTg-AD mouse models. (a) The total number of Pubmed citations for the two most popular AD mouse models, illustrates the rapid rise in reports utilizing the 5xFAD compared to the 3xTg-AD mouse models of AD. (b) When the Pubmed search criteria were further refined to only 5xFAD or 3xTg-AD with MRI, the number of citations dropped precipitously. Again, the 5xFAD mouse model has an increased utilization in neuroimaging studies (Pubmed search “5xFAD” or “3xTg” and then combined with “magnetic resonance imaging”).
Figure 1 Pubmed citations for 5xFAD and 3xTg-AD mouse models. (a) The total number of Pubmed citations for the two most popular AD mouse models, illustrates the rapid rise in reports utilizing the 5xFAD compared to the 3xTg-AD mouse models of AD. (b) When the Pubmed search criteria were further refined to only 5xFAD or 3xTg-AD with MRI, the number of citations dropped precipitously. Again, the 5xFAD mouse model has an increased utilization in neuroimaging studies (Pubmed search “5xFAD” or “3xTg” and then combined with “magnetic resonance imaging”).CC BY · PubMed Central
Figure 2 WT and transgenic female mice histological staining. (a) Staining in 5xFAD females at 18 months of age demonstrated a high load of β-amyloid plaques (Thioflavin-S) throughout the brain accompanied by elevated microglial activation (IBA-1) that was not observed in WT mice. (b) Staining for human Tau (HT7) as well as β-amyloid plaques (Thioflavin-S) in 18-month-old 3xTg-AD females revealed a more focal staining pattern compared to the 5xFAD model at the same age. Note the relative absence of β-amyloid plaques in the 3xTg-AD mice. Scale bar = 1 mm. (Images courtesy of K. Green, UCI MODEL-AD Consortium).
Figure 2 WT and transgenic female mice histological staining. (a) Staining in 5xFAD females at 18 months of age demonstrated a high load of β-amyloid plaques (Thioflavin-S) throughout the brain accompanied by elevated microglial activation (IBA-1) that was not observed in WT mice. (b) Staining for human Tau (HT7) as well as β-amyloid plaques (Thioflavin-S) in 18-month-old 3xTg-AD females revealed a more focal staining pattern compared to the 5xFAD model at the same age. Note the relative absence of β-amyloid plaques in the 3xTg-AD mice. Scale bar = 1 mm. (Images courtesy of K. Green, UCI MODEL-AD Consortium).CC BY · PubMed Central
Figure 3 Diffusion magnetic resonance imaging (dMRI) in 12-month-old female mice. Diffusion tensor imaging (DTI) parametric maps for axial diffusivity (AxD), radial diffusivity (RD), mean diffusivity (MD), fractional anisotropy (FA) and colored FA in females WT and 5xFAD at 12 months of age. Exemplar images at the level of the dorsal hippocampus illustrate changes in the corpus callosum and within the hippocampus.
Figure 3 Diffusion magnetic resonance imaging (dMRI) in 12-month-old female mice. Diffusion tensor imaging (DTI) parametric maps for axial diffusivity (AxD), radial diffusivity (RD), mean diffusivity (MD), fractional anisotropy (FA) and colored FA in females WT and 5xFAD at 12 months of age. Exemplar images at the level of the dorsal hippocampus illustrate changes in the corpus callosum and within the hippocampus.CC BY · PubMed Central

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Metadata

Authors
Jullienne, A., Trinh, M. V., & Obenaus, A.
Affiliations
  • University of California, Irvine (US)
  • Department of Pediatrics, University of California, Irvine, CA 92697, USA
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2022-01-28
Volume
10
Issue
2
Pages
305
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines10020305
PMC
PMC8869427
OpenAlex
W4210462365
Cited by
32
References
232
Citations by year
2026: 8 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 4
FWCI
0.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute on Aging (AG054345-01, AG054349-01)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, mouse models of Alzheimer's disease, 3xTg-AD mice, 5xFAD mice, magnetic resonance imaging, positron emission tomography, imaging biomarkers

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